Lower respiratory tract infection is a leading cause of morbidity and mortality in early childhood. These infections are primarily caused by viruses, such as respiratory syncytial virus (RSV), parainfluenzavirus (PIV) and influenza. Recently investigators in the Netherlands and Australia have described a new member of the Paramyxovirus family, tentatively named human Metapneumovirus (hMPV). The virus was associated with both upper and lower tract respiratory illness (LRI) but the epidemiology has not been studied. This study will investigate the incidence and clinical features of hMPV infection in children. The Vanderbilt Vaccine Clinic provides primary medical care to a large cohort of children who routinely have surveillance cultures of respiratory secretions and blood samples banked for serological studies. Hundreds of nasal wash and serum specimens are available for study, along with clinical data that has been prospectively collected in a blinded fashion by the study nurses. In small preliminary studies, we have used RT-PCR to identify hMPV in numerous frozen nasal wash specimens from children who previously tested negative for other known respiratory pathogens. The isolates share homology with the Netherlands strains, but show evidence of genetic diversity. Clinical symptoms associated with these infections were similar to RSV infection, characterized by fever, cough, wheezing and significant respiratory illness. A larger comprehensive study is needed. The specific aims of this study are to define the prevalence of hMPV infection in children, describe fully the spectrum of clinical illness and identify serologic markers of seroconversion and correlates of immunity. [unreadable] [unreadable] [unreadable]